Genetic mutation is associated with increased risk of death for patients with PTC

Presence of the genetic mutation BRAF V600E was significantly associated with increased cancer-related death among patients with papillary thyroid cancer (PTC), according to a new study. However, because overall mortality in PTC is low and the association was not independent of tumor characteristics, how to use this information to manage mortality risk in patients with PTC is unclear.

"Papillary thyroid cancer is the most common endocrine malignancy and accounts for 85% to 90% of all thyroid cancers," according to background information in the article, which was published in JAMA (2013;309[14]:1493-1501). "The overall 5-year patient survival rate for PTC is 95% to 97%. A major clinical challenge is how to reliably distinguish patients who need aggressive treatments to reduce mortality from those who do not. This represents a widely controversial issue in thyroid cancer medicine, particularly because of the low overall mortality of this cancer. The issue has become even more challenging given the high annual incidence of PTC."

BRAF V600E is a prominent oncogene in PTC and "has drawn considerable attention as a potential prognostic factor for PTC. However, the clinical significance of this mutation in PTC-related mortality has not been established."

Mingzhao Xing, MD, PhD, of the Johns Hopkins University School of Medicine, in Baltimore, Maryland, and colleagues conducted a study to examine and define the association between the BRAF V600E mutation and PTC-related mortality. The study included 1,849 patients (1,411 women and 438 men) with a median (midpoint) age of 46 years and an overall median follow-up time of 33 months after initial treatment at 13 centers in seven countries between 1978 and 2011.

The overall prevalence of BRAF V600E was 45.7% (845/1,849). There were 56 PTC-related deaths among the 1,849 patients, representing an overall mortality of 3%. Among these deaths, 45 cases (80.4%) were positive for BRAF V600E. The overall mortality of all PTC cases was 5.3% (45/845) in BRAF V600E-positive patients vs 1.1% (11/1,004) in mutation-negative patients.

When the aggressive tumor features of lymph node metastasis, extrathyroidal invasion, and distant metastasis were also included in the model, the association of BRAF V600E with mortality for all PTC was no longer significant, the authors wrote. "A higher BRAF V600E-associated patient mortality was also observed in several clinicopathological subcategories, but statistical significance was lost with adjustment for patient age, sex, and medical center."

"In summary, in this multicenter study, the presence of the BRAF V600E mutation was significantly associated with increased cancer-related mortality among patients with PTC. However, overall mortality in PTC is low, and the association was not independent of tumor behaviors. Therefore, how to use BRAF V600E for the management of mortality risk among patients with PTC is not clear. These findings support further investigation of the prognostic and therapeutic implications of BRAF V600E status in PTC."

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